Comprehensive Characterization of 98 Chinese Cases of Genetic Creutzfeldt-Jakob Disease With T188K Mutation

To characterize the demographic, clinical, and laboratory features of the Chinese patients of genetic Creutzfeldt-Jakob disease with T188K variant (T188K-gCJD), the most common subtype of genetic prion diseases (gPrDs) in China.

In this nationwide retrospective study, data from 98 genetically confirmed T188K-gCJD patients were collected via Chinese National Surveillance for CJD (CNS-CJD) from 2007 to 2025. The features of demography, clinical manifestations, MRI and EEG, cerebrospinal fluid (CSF) tests (14-3-3, CaM, RT-QuIC) and PRNP sequencing were comprehensively analyzed.

The onset ages of 98 Chinese T188K-gCJD patients ranged from 40 to 80 years old (y) (median: 61 years), with a male-to-female ratio of 1:0.85. The geographic distribution of T188K-gCJD patients showed a significant north-south disparity (cumulative incidence: 0.1217 vs. 0.0534 per million, p = 0.0227). Clinical phenotype of T188K-gCJD resembled closely that of sporadic CJD (sCJD), but positive rates of periodic sharp wave complexes (PSWC) on EEG (29.9%) and CSF RT-QuIC (53.2%) were relatively low. Majority of the patients progressed rapidly with the median survival of 5.0 months, which was associated only with a shorter onset-to-report interval.

The phenotype of T188K-gCJD is extremely similar to that of sCJD, underscoring the critical importance of PRNP sequencing for accurate diagnosis.